Chiral organic catalysts containing both a hydrogen bond donor and an acceptor can facilitate biomimetic 1,3-proton transfer catalysis to promote highly enantioselective olefin and imine isomerizations. These enantioselective isomerizations provide new access to valuable chiral building blocks such as α,β-unsaturated butenolides, α-amino acids, α,β-unsaturated cyclohexenones and trifluoromethylated amines. Catalysts such as dihydroquinine (DHQ) and dihydroquinidine (DHQD) have been developed for imine isomerizations and other asymmetric reactions such as Sharpless dihydroxylation. DHQ based catalysts afford one enantiomer, and DHQD catalysts give access to the opposite enantiomer. However, the high catalyst loading (10 mol %) and long reaction time (48-72 hours) has limited the application of this reaction in organic synthesis. DHQD catalysts often resulted in low enantioselectivity such that the S-enantiomer product is not readily accessed in this reaction. Scheme 1 summarizes the current state of the art in asymmetric isomerization of trifluoromethyl imines with acid-base bifunctional catalysts.

Thus, there is a need in the art to identify catalysts that can be used to promote imine isomerization reactions in high yield and enantiomeric excess. The presently disclosed compounds and methods meets this need.